The E. coli trp repressor is a ligand-mediated DNA binding protein, which regulates tryptophan biosynthesis at the transcriptional level. Upon binding two molecules of zwitterionic tryptophan, an allosteric conformational change occurs which converts the aporepressor from a non-specific to a sequence-specific DNA binding protein. The allosteric change alone is not sufficient for DNA binding: indole-3-propionate binds to the protein with a higher affinity than tryptophan, induces the conformational change, but yields a pseudorepressor which is unable to bind to DNA at all. In addition, while tryptophan analogues can alter the DNA binding affinity, several super-repressor mutants bind more tightly to DNA than the wildtype protein, in the absence of bound ligand. The trp repressor charge distribution is critical for DNA binding, since the protein has an overall -6 charge, yet binds with high affinity to a polyanion. The charge distribution, and therefore the electrostatic potential surface presented to DNA, can be altered by protein mutation and tryptophan analogue binding. The electrostatic potential surfaces for several protein crystal and model-built structures were related to experimental trends in binding affinities. From this work, we proposed a role for long-range electrostatic interactions in trp repressor-DNA association.